A review of over 60 cases of adult mastocytosis followed at the NIH, has substantiated the observation that mastocytosis can occur in distinctly different forms, or categories. We have, thus, instituted a new classification for mast cell disorders. Diseases of mast cell proliferation are now divided as follows: indolent mastocytosis, mastocytosis with dysmyelopoiesis, mast cell leukemia, and lymphadenopathic mastocytosis with eosinophilia. Each type of disease varies from other categories in its prognosis and treatment. Pediatric patients with urticaria pigmentosa or diffuse cutaneous mastocytosis often have systemic disease, as evidenced by the presence of a unique bone marrow lesion. These heretofore unrecognized lesions consist of focal collections of mast cells, eosinophils, and lymphocytes along small vessel endothelial cells. A double blind crossover trial comparing ketotifen, a mast cell stabilizing drug, and an H1 antihistamine; and hydroxyzine, an H1 antihistamine, has shown hydroxyzine to be more effective at lowering symptom scores. Neither drug affected plasma or urine histamine levels. Topical steroids lower the number of mast cells in skin and result in dramatic improvement in mastocytosis skin lesions. Dermal mast cells are increased 15-20 fold in patients with mastocytosis, and 2-3 fold in patients with idiopathic anaphylaxis or flushing. Mast cells first increase around endothelial cells.